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from psychological testing have been inconsistent.1e3 demented patients with MG seen at Sendai Medical
The frequency of depressive symptoms in patients with Center, Hanamaki General Hospital, Tohoku University
MG has also been inconsistently reported using different Hospital, Keio University Hospital, Tokyo Medical
measures.1e3 Although an intricate relationship to MG University Hospital and Tokyo Women’s Medical
appears to exist, previous studies were small scale and University Hospital from May until August 2010. To
did not clearly show causal backgrounds of depressive avoid a potential bias, we enrolled consecutive patients
symptoms in MG.1 2 during short duration (3 months). Patients with any
The present study evaluated self-reported symptoms of missing clinical data were excluded. All patients
depression in a sample of 287 patients with MG using provided written informed consent and were subjected
a standardised measure, the Beck Depression Inventorye to analysis. Clinical background data for the 287 patients
Second Edition (BDI-II),5 6 and systematically and with MG are shown in table 1.
statistically examined associations with detailed clinical The diagnosis of MG was based on clinical findings
parameters of MG. The purpose of this study was to (fluctuating symptoms with easy fatigability and recovery
clarify clinical factors associated with depressive state in after rest) with reductions in symptoms after intravenous
patients with MG. administration of anticholinesterase, decremental muscle
response to a train of low-frequency repetitive nerve
PATIENTS AND METHODS stimuli or the presence of antibodies against the acetyl-
Patients choline receptor of skeletal muscle (AChR-Ab) or against
This cross-sectional study was conducted at six neuro- muscle-specific tyrosine kinase (MuSK-Ab). Single-fibre
logical centres located in Eastern Japan (three in electromyography was not systematically examined. AChR-
Tohoku district and three in Tokyo area, East Japan MG Ab-negative cases comprised 55 of 287 patients. Two of the
study group). We evaluated 287 consecutive non- 55 AChR-Ab-negative patients were MuSK-Ab-positive.
Table 1 Backgrounds of patients and correlations of clinical factors with BDI-II score
Patient backgrounds
Clinical factors (287 in total) Correlation (95% CI) p Value
Age (years) 57.5617.1 0.05 (0.16 to 0.07) 0.200
Female* n¼193 0.19 (0.07 to 0.30) 0.001y
Time since onset (years) 8.968.3 0.08 (0.19 to 0.04) 0.10
Age at onset (years) 48.0618.6 0.01 (0.13 to 0.10) 0.41
Thymectomy* n¼141 0.02 (0.10 to 0.13) 0.39
Thymoma* n¼63 0.06 (0.05 to 0.18) 0.15
QMG 7.065.1 0.33 (0.22 to 0.43) <0.0001y
Ocular QMG 1.761.8 0.29 (0.17 to 0.39) <0.0001y
Bulbar QMG 0.360.8 0.14 (0.02 to 0.25) 0.01y
MG composite 5.865.7 0.40 (0.30 to 0.50) <0.0001y
MG-ADL 3.463.1 0.39 (0.29 to 0.49) <0.0001y
MGFA classification (worst)* I/II/III/IV/V: 0.17 (0.05 to 0.28) 0.002y
68/125/60/12/22
Current dose of PSL (mg/day) 4.665.9 0.33 (0.22 to 0.43) <0.0001y
Maximum dose of PSL (mg/day) 20.5620.7 0.02 (0.09 to 0.14) 0.34
Calcineurin inhibitors* n¼115 0.07 (0.04 to 0.19) 0.10
Crisis* n¼22 0.02 (0.10 to 0.14) 0.38
AChR-Ab positivity* n¼232 0.14 (0.25 to 0.02) 0.01y
Kv 1.4-Ab positivity* n¼37 0.05 (0.08 to 0.18) 0.22
Titin-Ab positivity* n¼53 0.09 (0.07 to 0.26) 0.10
MuSK-Ab positivity* n¼2 (of 55 AChR Not determined Not determined
Ab-negative patients)
CSR* n¼21 0.10 (0.22 to 0.01) 0.04y
PR* n¼22 0.09 (0.20 to 0.03) 0.08
MM* n¼95 0.17 (0.28 to 0.06) 0.002y
I* n¼91 0.12 (0.01 to 0.23) 0.02y
U* n¼54 0.13 (0.02 to 0.24) 0.01y
W* n¼4 0.03 (0.08 to 0.15) 0.28
*Pearson’s correlation or Spearman’s rank correlation.
yVariables entered into multivariate regression analysis (see the Results section in the text).
AChR-Ab, antibodies against acetylcholine receptor; BDI-II, Beck Depression InventoryeSecond Edition; CSR, complete stable remission;
I, improved; Kv1.4, voltage-gated potassium channel 1.4; MG, myasthenia gravis; MG-ADL, MG activities of daily living scale; MG composite,
MG composite scale; MGFA, Myasthenia Gravis Foundation of America; MM, minimal manifestations; MuSK, muscle-specific tyrosine kinase;
PR, pharmacologic remission; PSL, prednisolone; QMG, MGFA quantitative MG score; U, unchanged; W, worse.
symptoms and revealed current dose of oral PSL as the BDI-II score for patients with MG did not differ
most significant background for depressive state in MG. substantially from and overlapped with that of the
In fact, long-term use of corticosteroids has been Japanese standard. The frequency of individuals with
suggested to affect the brain and result in the develop- depressive state (BDI-II >21.5) was 13.6% in this study,
ment of depressive conditions.13e15 Complications of lower than that reported by Fisher et al.7 They reported
long-term corticosteroid use emerge at around 10 mg/ that moderate or worse depression (BDI-II >20 in the
day of prednisone or PSL.13e15 Consistently, mean dose original English version) was observed in 33% (15/45)
of oral PSL in patients with MG in depressive state was of patients with MG.7 The frequency of depressive
8.1 mg/day, significantly higher than that in patients symptoms in patients with MG has been inconsistent in
without depressive state (4.1 mg/day; p<0.001 using previous reports.13 Anxiety or depressive disorders have
ManneWhitney U test). Although oral corticosteroids been reported as more frequent among patients with
represent the first-line and most common agents for MG than in the general population.4 17 Conversely,
immunosuppressive treatment of MG,16 the present several authors have found no increased frequency of
results indicate a possible need for attention to dose and depression among patients with MG compared to the
associated depressive side effects. The constant need for general population.18e20 Regarding such discrepancies,
medication itself might also cause psychological stress, given that the present study showed depressive symp-
but use of calcineurin inhibitors (ie, cyclosporine toms to be positively correlated with both severity of MG
microemulsion and tacrolimus) was not associated with and corticosteroid dose, frequency of depressive patients
depressive state. In Japan, oral cyclosporine micro- with MG may alter depending on such background
emulsion (2.0e5.0 mg/kg/day) was divided into two factors in subjects.
doses taken at intervals of 12 h, and oral tacrolimus The present analysis revealed that unchanged status
(3.0e4.0 mg/day) was given once a day. There may be despite treatment and early disease stage are also signif-
some differences of prescription pattern among Japan icant background factors for depressive state, along with
and other countries. disease severity. These findings suggest that achieving
15. Brown ES, Suppes T. Mood symptoms during corticosteroid therapy: 18. Doering S, Henze T, Schüssler G. Coping with myasthenia gravis and
a review. Harv Rev Psychiatry 1998;5:239e46. implications for psychotherapy. Arch Neurol 1993;50:617e20.
16. Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: 19. Paul RH, Nash JM, Cohen RA, et al. Quality of life and well-being
emerging clinical and biological heterogeneity. Lancet Neurol of patients with myasthenia gravis. Muscle Nerve 2001;24:
2009;8:475e90. 512e16.
17. Magni G, Micaglio GF, Lalli R, et al. Psychiatric disturbances 20. Paul RH, Cohen RA, Goldstein JM, et al. Severity of mood, self-
associated with myasthenia gravis. Acta Psychiatr Scand evaluative, and vegetative symptoms of depression in myasthenia
1988;77:443e5. gravis. J Neuropsychiatry Clin Neurosci 2000;12:499e501.
Section/Topic Item
Recommendation Reported on page #
#
Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract Page 1
(b) Provide in the abstract an informative and balanced summary of what was done and what was found Page 3
Introduction
Background/rationale 2 Explain the scientific background and rationale for the investigation being reported Page 5
(b) Describe any methods used to examine subgroups and interactions Not applicable
(c) Explain how missing data were addressed Page 6
(d) If applicable, describe analytical methods taking account of sampling strategy Not applicable
(e) Describe any sensitivity analyses Not applicable
Results
Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially eligible, examined for eligibility, Not applicable
confirmed eligible, included in the study, completing follow‐up, and analysed
(b) Give reasons for non‐participation at each stage Not applicable
(c) Consider use of a flow diagram Not applicable
Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential Table 1
confounders
(b) Indicate number of participants with missing data for each variable of interest Page 6;
Not applicable
Outcome data 15* Report numbers of outcome events or summary measures Not applicable
Main results 16 (a) Give unadjusted estimates and, if applicable, confounder‐adjusted estimates and their precision (eg, 95% confidence Not applicable
interval). Make clear which confounders were adjusted for and why they were included
(b) Report category boundaries when continuous variables were categorized Page 10
(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period Not applicable
Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and sensitivity analyses Not applicable
Discussion
Key results 18 Summarise key results with reference to study objectives Pages 12‐13
Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and Page 4 (ARTICLE
magnitude of any potential bias SUMMARY)
Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from Pages 12‐13
similar studies, and other relevant evidence
Generalisability 21 Discuss the generalisability (external validity) of the study results Pages 12‐13
Other information
Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on Page 14
which the present article is based
*Give information separately for cases and controls in case‐control studies and, if applicable, for exposed and unexposed groups in cohort and cross‐sectional studies.
Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and published examples of transparent reporting. The STROBE
checklist is best used in conjunction with this article (freely available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at
http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is available at www.strobe‐statement.org.